New platform vaccines for immuno-therapeutic or prophylactic applications
An ongoing collaboration between Melbourne-based Biotech company Sementis Ltd. and the Experimental Therapeutics Laboratory, has developed a novel vaccine vector platform. This platform is a Vaccinia virus-based live viral vector, and through complicated genetic reformation, the virus has been re-created and aims to be a safer and more efficient vaccine delivery system. By modifying immune-related genes, this live viral vector aims to efficiently express the target antigen, and effectively induce the immune response. More importantly, by controlling virus essential replication-related genes, the vector is designed to have an extremely safe profile. In addition, this vector system can accommodate large sizes of foreign antigen genes and can therefore be used for a range of immunotherapeutic applications, such as allergies, cancer and infectious diseases
Some cancers contains cells that are biochemically distinct from normal cells. We are investigating ways to use this information to develop recombinant viral vaccines that will ‘teach’ the immune system to attack cells based on the presence of these distinct molecules. The development of such a vaccine would enable us to treat and prevent cancers without harming surrounding normal tissues and could be used to improve the outcomes of current therapies. We are currently particularly interested in applying this strategy to prostate cancer and melanoma.
A vaccine for Zika virus infection
The Experimental Therapeutics Laboratory’s collaboration with Sementis Ltd. is working to develop a vaccine to combat the mosquito-borne Zika virus, which is now a public health emergency of international concern, according to the World Health Organization. Zika virus is transmitted by the same group of mosquitoes that spread the Dengue and Chikungunya viruses, but is of particular concern owing to its association with birth defects (microcephaly) and Guillain-Barré syndrome. UniSA and Sementis Ltd. have developed a protective vaccine for mosquito-borne Chikungunya virus which has been shown effective in preclinical studies. The same vaccine delivery system is being utilized to develop a vaccine for Zika virus with preclinical laboratory experiments currently underway.
A new vaccine for Chikungunya virus infection
Chikungunya is a mosquito-borne infectious disease capable of causing long term, debilitating, arthritis-like symptoms and even death in severe cases. Mutation and climate changes have increased the mosquito host range and distribution, and outbreaks are on the increase. A vaccine is greatly needed in regions where Chikungunya is spreading as well as protection for travelers in those affected areas. In conjunction with the QIMR Berghofer Medical Research Institute, the Sementis viral vector platform is being utilised as a vaccine for Chikungunya, and has been proven to provide complete protection from infection in pre-clinical trials.
The effect of inflammation on reproductive success
The Experimental Therapeutics Laboratory research group and collaborative partner Dr Kerrilyn Diener and Professor Sarah Robertson, have an interest in studying the innate and adaptive immune systems within the female reproductive tract. This is in an attempt to understand their role in dictating the outcome of many conditions including the response to vaccination, infection and pregnancy. The group are currently investigating the role of infection, tolerance and plasmacytoid dendritic cells during different stages of the reproductive cycle and pregnancy to determine whether early infection, or depletion of plasmacytoid dendritic cells throughout pregnancy, can adversely affect the outcomes of implantation and pregnancy and ultimately fetal growth, survival and long term behavioural outcomes.
Immunotherapeutics to treat and prevent Tasmanian devil facial tumour disease
The Experimental Therapeutics Laboratory research group and in collaboration with Professor Greg Woods and Dr Bruce Lyons are currently developing cancer therapeutics to treat the Tasmanian devil facial tumour disease and also to treat cancer in dogs. The immunotherapeutics aim is to block inhibitory checkpoint molecules CTLA4 and PD-1, a strategy which has yielded unprecedented success in treating stage IV human cancers. Additionally, one of the primary means by which the devil facial tumour evades the immune system is via downregulation of MHC class I on tumour cells. We are developing devil facial tumour cell lines that produce IFNγ, which should stimulate expression of MHC class I. These modified tumour cell lines can be used as part of a therapeutic vaccine. These projects have the potential to help save an endangered species, develop new veterinary therapeutics that could become widely used in veterinary medicine, and shed light on how cancer evades the immune system. Students involved in cancer therapeutic design will develop basic molecular biology, immunology, cell culture and genetic engineering skills that will prepare them well for a career in the biomedical sciences.
Immunotherapeutics to treat and prevent peanut allergy and other food allergies
Despite the risk of potentially fatal reactions, there is currently no method available in routine clinical practice for treating peanut allergies. The Experimental Therapeutics Laboratory research group have established a robust murine peanut-induced anaphylaxis model that will be used to test an immunotherapeutic approach which aims to selectively inhibit the production of peanut allergen-specific antibodies and decreases the risk of anaphylaxis during the desensitization process. Together with collaborative partner Dr William Smith we are determining whether this type of immunotherapy could have broad application in treating allergic diseases.
The role of damage associated molecular patterns in sepsis, cancer and autoimmunity
The overall aim of these studies is to understand the role of an important protein called HMGB1 in sepsis and cancer. A better understanding of its role will enable more precise application of a new kind of antibody that can neutralise activity of HMGB1. Sepsis (or overwhelming infection) often causes death in the intensive care unit and may complicate common anti-cancer treatments such as chemotherapy. HMGB1 is secreted during serious infection and can mediate its harmful effects. Blocking HMGB1 activity with antibody can prevent this happening in animal models. We are developing and testing neutralising antibodies against HMGB1 that could ameliorate clinical course of sepsis in the hospital, both in adults (with collaborative partner Associate Professor Marianne Chapman) and infants (with collaborative partners Associate Professor Michael Stark and Dr Nicki Hodyl). HMGB1 can be secreted by dead and dying cancer cells and push cancer cells toward a type of cell death called autophagy, which can promote resistance to commonly used anti-cancer agents. With collaborative partner Professor Michael Brown, we are blocking HMGB1 activity with antibody which may overcome the development of autophagy, helping anti-cancer drugs work better to kill cancer cells. We are also interested in the role that HMGB1 and other damage-associated molecular patterns play in the pathogenesis of autoimmune diseases including in myositis, in collaboration with Dr Vidya Limaye.
Manipulating the inflammatory response to biomaterial implants
New clinical applications for biomaterial implants are rapidly emerging, and novel approaches to their manufacture and the material from which they will be constructed from are warranted. This is because they need to be able to interact favourably with the body’s defence systems and this project aims to achieve this goal using nanotechnology. With collaborative partner Associate Professor Krasimir Vasilev, we aim to provide a mechanistic understanding of how surface nanotopography affects inflammatory responses. We have experimental evidence demonstrating that engineered surface nanotopography in combination with surface chemistry downregulates the expression of proinflammatory cytokines from primary macrophages. These exciting findings are important because they show that it may be possible to engineer the nanotopography of a biomedical device surface in a manner which leads to a desired and predictable level of inflammation and subsequent foreign body reaction (FBR) medical implants and tissue engineering constructs.
Advanced materials for water solutions
As a vital resource it is important that everyone if afforded access to clean and safe water. Research currently underway is looking at solutions to maximize water use efficiency and availability to secure this resource into the future. Advanced materials aimed at detecting and removing water based toxins and pathogens are currently being developed in collaboration with Dr. Sally Plush and the industry partner Puratap. It is envisaged that this research will deliver cost effective solutions for water purification and quality determination.